Antifungal agents

Abstract

A pine root (Deutero mycetes) fungal metabolite and analogs thereof having antifungal activity.

What is claimed is: 
     
       1. A method of treating a fungal infection in a patient, comprising administering to the patient an effective amount of pharmaceutical composition comprising a compound having the formula (VI): ##STR7## wherein each of R 1  and R 2  is independently selected from H, C 1-10  alkyl, C 1-10  alkoxy, C 2-10  alkenyl, C 2-10  alkenoxy, C 6-10  aryl, substituted or unsubstituted C 6-10  alkylcarbonyloxy, and C 2-10  acyloxy; or R 1  and R 2  taken together are ═O or substituted or unsubstituted C 1-10  alkylenedioxy, carbonyldioxy, and other carbonyl-protecting groups; when there is no double bond between C-7 and C-11, each of R 3 , R 4  and R 5  is independently selected from C 1-10  alkyl, C 1-10  alkoxy, and C 1-10  acyloxy; or R 4  and R 5  taken together are ═O, C 1-10  alkylidene, or C 1-10  alkenylidene; and when there is a double bond between C-7 and C-11, R 3  and R 4  are independently selected from C 1-10  alkyl, C 1-10  alkoxy and C 1-10  acyloxy; and R 5  is absent;   R 6  is C 1-10  alkylamino or C 1-10  alkylthio when there is no double bond between C-9 and C-10; R 6  is absent when there is a double bond between C-9 and C-10;   X is H, OH, OR p  where R p  is C 1-10  alkyl, C 6-10  aryl, C 2-10  acyl, C 6-10  arylcarbonyl, tri(C 1-6  alkyl)silyl, and other hydroxy-protecting groups, or Y having the formula: ##STR8## Z is --(C═O)--NH--, --(C═O)--O--, or --O--; and each of r a  -r h  is independently selected from H, methyl, halomethyl, hydroxy, and OR p , where R p  is C 1-10  alkyl, C 6-10  aryl, C 2-10  acyl, C 6-10  arylcarbonyl, and other hydroxy-protecting groups, provided that at least two of r a  -r h  are hydroxyl groups which do not form a gem-diol;   provided that where X is OH, --C(R 3 ) (R 4 ) (R 5 ) is neither isopropenyl nor isopropylidene; where X is O-(trialkylsilyl), --C(R 3 ) (R 4 ) (R 5 ) is not 2-hydroxylisopropyl; and provided that when R 1 , R 2 , and X are H, --C(R 3 ) (R 4 ) (R 5 ) is not isopropenyl;   or a pharmaceutically acceptable salt thereof and a pharmaceutically-acceptable carrier, thereby treating said fungal infection.   
     
     
       2. A method of claim 1, wherein one of r a  and r b  is methyl, one of r c  and r d  is hydroxyl, one of r e  and r f  is H, and one of r g  and r h  is hydroxyl and the other is methyl. 
     
     
       3. A method of claim 1, wherein at least three of r a  -r h  are hydroxyl and at least two of the remaining of r a  -r h  are methyl. 
     
     
       4. A method of claim 1, wherein the patient is a mammal. 
     
     
       5. A method of claim 4, wherein the mammal is a human.